|Inhalant, Systemic, and Topical
Corticosteroids increase renal calcium excretion and decrease intestinal
calcium absorption (Gennari 1993; Lems et al. 1998). By altering normal calcium
metabolism and reducing osteoblast activity, corticosteroids increase not only
bone loss, but the risk for developing osteoporosis as well (Nielson et al.
1988; Reid and Ibbertson 1986).†
Osteoporosis is the primary disease associated with chronic calcium
deficiency; it can result in pathologic fractures associated with bone pain,
spinal deformity, and premature morbidity and mortality (Cashman and Flynn 1999;
Covington 1999). Other signs and symptoms of depleted serum calcium levels
include arrhythmias, neuromuscular irritability, and mental status changes such
as depression and psychosis (Potts 1998).
Calcium supplementation in the form of citrate, malate, gluconate, or
carbonate salts may range from 1000 mg to 1500 mg or more daily (Adler and Rosen
1999; Covington 1999). Doses as high as 3000 mg/day with 10 to 50 mcg/day of
25-OH-D3 may be appropriate if plasma calcium and phosphate levels are stable
and within normal range (DrŁeke 1999). In cases where calcium deficits are
associated with vitamin D deficiency, up to 6000 mg/day of calcium (acetate or
carbonate) may be warranted. These values should be adjusted on an individual
basis depending upon the patient's age, gender, clinical presentation, serum
calcium levels, dietary habits, and medication regimen. Calcium replacement
should be part of a comprehensive approach to the evaluation and treatment of
Long-term treatment with corticosteroids suppresses DHEA production in
post-menopausal women (Smith et al. 1994).
Decreased plasma levels of DHEA have been linked to various pathologies such
as certain cancers, cardiovascular disorders, inflammatory diseases, and type II
diabetes mellitus (Hinson and Raven 1999).
Daily doses of 50 mg in patients aged 40 to 70 years produced DHEA levels
equivalent to those found in young adults within 2 weeks of initiation of
replacement therapy (Morales et al. 1994). These levels were maintained for 3
months of the study and patients reported improvements in their general sense of
physical and psychological well-being; no side effects were associated with DHEA
therapy at this dose. It has been suggested that doses should not exceed 25
mg/day for women or 50 mg/day for men (Huppert et al. 2000). Long-term safety
and efficacy of DHEA supplementation has not been established (Murray and
Corticosteroids reduce magnesium levels in serum and bone (Atkinson et al.
1998; Rolla et al. 1990; Simeckova et al. 1985).
Magnesium deficiency affects calcium and vitamin D metabolism and is
primarily associated with hypocalcemia (Cashman and Flynn 1999). Clinically,
neuromuscular hyperexcitability may be the first symptom manifested in patients
with hypomagnesemia (reflected in a serum concentration of 17 mg/L or less).
Recent evidence supports a possible connection between chronically low magnesium
levels and various illnesses such as cardiovascular disease, hypertension,
diabetes, and osteoporosis.
The current recommended dietary allowance (RDA) for magnesium ranges from 30
to 420 mg/day, depending upon age and gender (Cashman and Flynn 1999). For
replacement therapy, doses should be tailored to the patient's clinical
condition, taking into account serum magnesium levels, dietary habits, and
Corticosteroids may reduce nocturnal melatonin levels (Demisch et al.
Alterations in melatonin levels have been associated with disturbances in the
sleep-wake cycle and jet lag (Avery et al. 1998).
Optimal doses for melatonin therapy have not been established (Avery et al.
1998). Commonly available doses range from 0.3 to 5 mg. Physiological blood
levels are achieved with doses of 0.3 mg; higher doses (1 mg) result in
supraphysiological levels of melatonin in the blood. The efficacy of melatonin
supplementation is dependent upon the time of administration, as effects are
related to circadian rhythms.
Note: Corticosteroid effects on the immune system may be modulated by
melatonin (Rogers et al. 1997). In vitro, the combination of melatonin and
corticosteroids produced significantly greater suppression of lymphocyte
proliferation than corticosteroids alone.
Corticosteroids enhance potassium excretion (Adam et al. 1984; Stanton et al.
Potassium depletion as a consequence of prolonged drug therapy is usually
associated with chloride deficiency and manifests as hypokalemic, hypochloremic
metabolic acidosis (Covington 1999). Signs and symptoms of deficiency include
anorexia, apprehension, drowsiness, listlessness, fatigue, nausea, muscle cramps
and weakness, tetany, excessive thirst, altered mental status, and irrational
behavior. Severe hypokalemia could also result in clinical manifestations of
cardiac arrythmia, including primarily palpitations, cardiac arrest, and death.
A loss from total body stores of approximately 100 to 200 mEq of potassium is
usually required to cause a decrease in serum potassium levels of 1
The usual range of treatment is 20 to 100 mEq/day of potassium (PDR 2000).
The appropriate doses for replacement therapy should be determined on an
individual basis, considering the patient's age, gender, clinical presentation,
serum potassium levels, dietary habits, and medication regimen. The chloride
salt is appropriate treatment for cases of alkalosis (Covington 1999). In cases
of acidosis, other potassium salts such as bicarbonate, citrate, acetate, or
gluconate are preferred.
|Protein & Amino
Corticosteroids may cause protein wasting (Garrel et al.
Deficiencies of protein are characterized by compromised immune status,
generalized decreases in function and strength, apathy, weight loss, increased
susceptibility to infection, impaired wound healing, and growth retardation in
children (Covington 1999). Severe depletion may be characterized by muscle
wasting, deterioration in skin and hair, decreased heart rate, blood pressure,
and body temperature.
Nutritional repletion through dietary means is the preferred treatment
approach in cases of protein depletion or deficiency (Covington 1999). Adopting
a balanced diet consisting of high levels of calories, protein, vitamins, and
minerals is one option available for the treatment of patients with depleted
levels of protein. Oral or parenteral supplementation offers another therapeutic
approach to restore nutritional status, maintain caloric intake, and achieve
recommended dietary allowances for protein (generally 600 to 800 mg/kg protein)
(Reeds and Beckett 1996).
Corticosteroids may deplete selenium levels (Peretz et al. 1987).
Selenium deficiency may lead to oxidative DNA damage (Ames 2000). Chronically
low levels of this trace element are associated with pathologies such as
cardiovascular disease, rheumatic disorders, muscle, and digestive problems
(Navarro-Alarcon and Lopez-Martinez 2000). In addition, there may be a
connection between depleted selenium levels and cancer, cirrhosis, and
The recommended dietary allowance (RDA) for selenium ranges from 0.70 to 3.50
mg/day (Ames 2000). Doses of 0.02 to 0.05 mg/day have been suggested to prevent
selenium deficiency and its associated disorders (Navarro-Alarcon and
Lopez-Martinez 2000). Optimal and toxic levels of this nutrient have not been
established (Ames 2000). Selenium supplementation may play a role in cancer
prevention, including prostate, breast, colon, and cervical carcinoma.
Corticosteroids may deplete vitamin B6 levels (Sur et al. 1993).
Usually, vitamin B6 deficiency is accompanied by depletions of other B
vitamins (National Research Council 1989). Signs and symptoms of low levels of
this vitamin include epileptiform convulsions with abnormal EEG findings,
dermatitis, anemia, weakness, mental confusion, irritability, nervousness,
insomnia, and abnormal tryptophan metabolism (Covington 1999; National Research
Council 1989; Wilson 1998). Depleted levels may increase the risk of colon and
prostate cancers, heart disease, brain dysfunction, and birth defects (Ames
Neuropathology resulting from vitamin B6 deficiency should be treated with
doses of 50 to 200 mg/day (Covington 1999). Dietary deficiency usually responds
to doses of 10 to 20 mg/day. Doses should be tailored to account for the
patient's age, gender, clinical presentation, serum vitamin B6 levels, dietary
habits, and medication regimen.
Corticosteroids may deplete folic acid levels (Frequin et al. 1993).
Low levels of folate have been linked to colon cancer, heart disease,
cognitive deficits, and birth defects, specifically neural tube defects (Ames
2000; Covington 1999). Deficiency increases chromosome breakage and elevates
serum homocysteine. Vitamin B9 deficiency may also lead to megaloblastic
The recommended dietary allowance (RDA) for adults is 300 to 600 mcg/day
(Covington 1999). However, recommendations of doses of folic acid as high as
2000 mcg/day have been reported in the literature (Mayer et al. 1996). For
replacement therapy, doses should be based upon the patient's individual needs,
considering the clinical presentation, serum folate levels, age, gender, dietary
habits, and medication regimen.
Corticosteroids may deplete vitamin B12 levels (Frequin et al. 1993).
Symptomatic vitamin B12 deficiency is rare because complications may appear
only after the deficiency has existed for 10 to 15 years (Berger 1985;
Carpentier et al. 1976). Low vitamin B12 levels could increase the risk of colon
cancer, heart disease, brain dysfunction, birth defects, and irreversible
neuropathy (Ames 2000; Covington 1999). Irritability, weakness, numbness,
fatigue, glossitis, anorexia, headache, palpitations, and altered mental status,
including personality and behavioral changes, are some of the signs and symptoms
of vitamin B12 depletion (Covington 1999). Prolonged deficiency leads to
pernicious or megaloblastic anemia that may be associated with leukopenia and
Doses of 25 to 250 mcg/day of vitamin B12 have been used to correct
nutritional deficiency (Covington 1999). Oral doses between 500 to 1000 mcg/day
have been recommended for the treatment of pernicious anemia (Carmel 2000).
Replacement therapy should be based on the patient's individual needs,
considering the clinical presentation, serum B12 levels, age, gender, dietary
habits, and medication regimen.
Corticosteroids may inhibit cellular uptake of ascorbic acid and reduce
concentrations in the aqueous humor and testicular tissues (Chowdhury and Kapil
1984; Levine and Pollard 1983; Mehra et al. 1982).
Patients with depleted levels of vitamin C may present with anemia, icterus,
edema, lethargy, fatigue, fever, ecchymoses, hypotension, convulsions, gum
disorders, tooth loss, emotional changes, and perifollicular hyperkeratotic
papules (Carr and Frei 1999; Covington 1999; National Research Council 1989;
Wilson 1998). In addition, they may exhibit signs of poor wound healing,
increased susceptibility to infection, and markedly defective collagen
synthesis. Severe deficiency results in scurvy, which is potentially fatal (Carr
and Frei 1999; National Research Council 1989; Wilson 1998). Scurvy involves
degenerative changes in capillaries, bone, and connective tissue, resulting in
clinical symptoms that include weakness, joint tenderness and swelling, and
spontaneous hemorrhages (Carr and Frei 1999; Covington 1999; National Research
Council 1989; Wilson 1998). Patients with vitamin C deficiency may also be at
increased risk of developing cataracts and heart disease (Ames
Treatment of scurvy requires doses between 300 and 1000 mg/day for adults
(Covington 1999). Other recommendations range from the recommended dietary
allowance (RDA) of 60 mg to 2000 mg/day for adults (Carr and Frei 1999; Wilson
1998). One study proposes that no adult receive more than 1000 mg/day because
higher doses could cause nausea and diarrhea (Ausman 1999). To minimize the
possibility of gastric upset, buffered and sustained-release vitamin C
preparations are recommended. Specific doses account for the patient's age,
gender, overall health status, dietary habits, and medication regimen. Smokers
must consume 2 to 3 times more vitamin C than non-smokers (Ames
Corticosteroid therapy reduces serum 1,25-dihydroxyvitamin-D3 in children
(Chesney et al. 1978).
Because vitamin D is fat-soluble, prolonged periods of deficiency are
required to produce symptoms (National Research Council 1989). While the long
evolution is often asymptomatic (Rao 1999), depleted levels are characterized by
inadequate mineralization of the bone, which could lead to rickets (in children)
and osteomalacia (in adults) (Covington 1999; National Research Council 1989;
Rao 1999). Other signs and symptoms of low levels of vitamin D include increased
risk of fractures, osteoporosis, phosphaturia, hyperparathyroidism, chronic
muscle weakness, hypovitaminosis D, bone pain, pseudofractures, waddling gait,
or severe, chronic hypocalcemia (Holick et al. 1998; National Research Council
1989; Rao 1999; Vieth 1999). Subclinical vitamin D deficiency has been reported
in postmenopausal women with osteoporosis (Rao 1999). The prevalence of vitamin
D deficiency is more common in women, certain ethnic populations, and increases
Coadministration of vitamin D with calcium offsets the bone loss induced by
chronic corticosteroid therapy (Frauman 1996; Hachulla and Cortet 1998; Weryha
et al. 1998). Doses of vitamin D3 ranging from 1000 to 2000 IU/day or 25-OH-D3
ranging from 10 to 25 mcg/day have been used to treat vitamin D deficiency,
which is characterized by low plasma levels of 25-OH-D3 (DrŁeke 1999). Other
recommendations involve doses between 200 to 800 IU/day for adults (Rao 1999)
and 50,000 IU/month for elderly patients with osteomalacia (Holick et al. 1998).
Corticosteroids alter zinc metabolism and can cause depletion (Flynn et al.
1971; Fodor et al. 1975; Fontaine et al. 1991; Yunice, et al.
Clinically, signs and symptoms of zinc deficiency include alopecia,
dermatitis, diarrhea, growth retardation, increased susceptibility to infection,
and loss of appetite or sense of taste (Ames 2000; Falchuk 1998). Severe zinc
deficiency further impacts dermatologic, gastrointestinal, immune, nervous,
reproductive, respiratory, and skeletal systems (Ames 2000; Hambidge 2000).
Doses of zinc up to 50 mg/day may be recommended (Hambidge 2000). This upper
limit includes an adult's total daily intake, which may be higher than
anticipated because of the increasing trend to fortify foods with zinc. It is
important to be mindful of this limit, even if decisions are deliberately made
to temporarily exceed this level for anticipated pharmacological
This information is intended to serve as a concise reference for healthcare
professionals to identify substances that may be depleted by many commonly
prescribed medications. Depletion of these substances depends upon a number of
factors including medical history, lifestyle, dietary habits, and duration of
treatment with a particular medication. The signs and symptoms associated with
deficiency may be nonspecific and could be indicative of clinical conditions
other than deficiency. The material presented in these monographs should not in
any event be construed as specific instructions for individual
Adam WR, Goland GJ, Wellard RM. Renal potassium adaptation in the rat: role
of glucocorticoids and aldosterone. Am J Physiol. 1984;246(3 Pt
Adler RA, Rosen CJ. Glucocorticoids and osteoporosis. Endocrinol Metab
Clin North Am. 1999;23:641-654.
Ames BN. Micronutrient deficiencies: A major cause of DNA damage. Ann NY
Acad Sci. 2000;889:87-106.
Atkinson SA, Halton JM, Bradley C, Wu B, Barr RD. Bone and mineral
abnormalities in childhood acute lymphoblastic leukemia: influence of disease,
drugs and nutrition. Int J Cancer Suppl. 1998;11:35-39.
Ausman LM. Criteria and recommendations for vitamin C intake. Nutr
Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann
Berger W. Incidence of severe side effects during therapy with sulfonylureas
and biguanides. Horm Metab Res Suppl. 1985;15:111-115.
Carmel R. Current concepts in cobalamin deficiency. Ann Rev Med.
Carpentier JL, Bury J, Luyckx A, Lefebvre P. Vitamin B12 and folic acid serum
levels in diabetics under various therapeutic regimens. Diabetes Metab.
Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C
based on antioxidant and health effects in humans. Am J Clin Nutr
Cashman K, Flynn A. Optimal nutrition: calcium, magnesium and phosphorus.
Proc Nutr Soc. 1999;58:477-487.
Chesney RW, Maxess RB, Harnstra AJ, et al. Reduction of
serum-1,12-dihydroxyitamin- D3 in children receiving glucocorticoids.
Chowdhury AR, Kapil N. Interaction of dexamethasone and
dehydroepiandrosterone on testicular ascorbic acid and cholesterol in
prepubertal rat. Arch Androl. 1984;12(1):65-67.
Covington T, ed. Nonprescription Drug Therapy Guiding Patient
Self-Care. St Louis, MO: Facts and Comparisons; 1999:467-545.
Demisch L, et al. Influence of dexamethasone on nocturnal melatonin
production in healthy adult subjects. J Pineal Res.
DrŁeke T. Medical management of secondary hyperparathyroidism in uremia.
Am J Med Sci. 1999;317(6):383-389.
Falchuk KH. Disturbances in Trace Elements. In: Fauci A, Braunwald E,
Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine.
14th ed. New York, NY: McGraw-Hill Companies Health Professional
Flynn A, Pories WJ, Strain WH, et al. Rapid serum-zinc depletion associated
with corticosteroid therapy. Lancet. 1971;2(7735):1169-1172.
Fodor L, Ahnefeld FW, Fazekas AT. [Studies on the glucocorticoid control of
zinc metabolism]. Infusionsther Klin Ernahr.
Fontaine J, Neve J, Peretz A, et al. Effects of acute and chronic
prednisolone treatment on serum zinc levels in rats with adjuvant arthritis.
Agents Actions. 1991;33(3-4):247-253.
Frauman AG. An overview of the adverse reactions to adrenal corticosteroids.
Adverse Drug React Toxicol Rev. 1996;15(4):203-206.
Frequin ST, et al. Decreased vitamin B12 and folate levels in cerebrospinal
fluid and serum of multiple sclerosis patients after high-dose intravenous
methylprednisolone. J Neurol. 1993;240(5):305-308.
Garrel DR, Delmas PD, Welsh C, et al. Effects of moderate physical training
on prednisone-induced protein wasting: a study of whole-body and bone protein
metabolism. Metab. 1988;37(3):257-262.
Gennari C. Differential effect of glucocorticoids on calcium absorption and
bone mass. Br J Rheumatol. 1993;32(Suppl 2):11-14.
Hachulla E, Cortet B. [Prevention of glucocorticoid induced osteoporosis].
Rev Med Interne. 1998;19(7):492-500.
Hambidge M. Human zinc deficiency. J Nutr. 2000;130(5S
Hinson JP, Raven PW. DHEA deficiency syndrome: a new term for old age? J
Holick MF, Krane SM, Potts JT. Calcium, phosphorus, and bone metabolism:
calcium-regulating hormones. In: Fauci AS, Braunwald E, Isselbacher KJ, et al,
eds. Harrison's Principles of Internal Medicine. 14th ed. New
York: McGraw-Hill Companies Health Professional Division; 1998:2221-2222.
Huppert FA, Van Niekerk JK, Herbert J. Dehydroepiandrosterone (DHEA)
supplementation for cognition and well-being. Cochrane Database Syst Rev
Lems WF, Jacobs JW, Netelenbos JC, et al. [Pharmacological prevention of
osteoporosis in patients on corticosteroid medication]. Ned Tijdschr
Levine MA & Pollard HB. Hydrocortisone inhibition of ascorbic acid
transport by chromaffin cells. FEBS Lett. 1983;158(1)L134-L138.
Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis.
J Am Coll Cardiol. 1996;27(3):517-527.
Mehra KS, Kumar A, Dubey SS, Palodhi GR. The effect of vitamin A and
cortisone on ascorbic acid content in the aqueous humor. Ann Ophthalmol.
Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of
dehydroepiandrosterone in men and women of advancing age. Endocrinol
Murray M, Pizzorno J. Encyclopedia of Natural Medicine. 2nd
ed. Rocklin, CA: Prima Publishing; 1998.
National Research Council. Recommended Dietary Allowances.
10th ed. Washington, DC: National Academy Press; 1989.
Navarro-Alarcon M, Lopez-Martinez MC. Essentiality of selenium in the human
body: relationship with different diseases. Sci Total Environ.
Nielson HK, Charles P, Mosekilde L. The effect of single oral doses of
prednisone on the circadian rhythm of serum osteocalcin in normal subjects. J
Clin Endocrinol Metab. 1988;67(5):1025-1030.
Peretz A, Neve J, Vertongen F, et al. Selenium status in relation to clinical
variables and corticosteroid treatment in rheumatoid arthritis. J
Physicians' Desk Reference, 54th ed. Montvale, NJ:
Medical Economics Company; 2000:459.
Potts JT. Diseases of the parathyroid gland and other hyper- and hypocalcemic
disorders. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's
Principles of Internal Medicine. 14th ed. New York: McGraw-Hill
Companies Health Professional Division; 1998:2241.
Rao DS. Perspective on assessment of vitamin D nutrition. J Clin
Reeds P, Beckett P. Protein and amino acids. In: Ziegler E, Filer LJ, eds.
Present Knowledge in Nutrition. 7th ed. Washington, DC:
International Life Sciences Institute; 1996:67-86.
Reid IR, Ibbertson HK. Calcium supplements in the prevention of
steroid-induced osteoporosis. Am J Clin Nutr. 1986;44(2):287-290.
Rogers N, van den Heuvel C, Dawson D. Effect of melatonin and corticosteroid
on in vitro cellular immune function in humans. J Pineal Res.
Rolla G, Bucca C, Bugiani M. Hypomagnesemia in chronic obstructive lung
disease: effect of therapy. Magnes Trace Elem. 1990;9(3):132-136.
Simeckova A, Neradilova M, Reisenauer R. Effect of prednisolone on the rat
bone calcium, phosphorus and magnesium concentration. Physiol Bohemoslov.
Smith BJ, et al. Does beclomethasone dipropionate suppress
dehydroepiandrosterone sulfate in postmenopausal women? Aust N Z J Med.
Stanton B, Giebisch G, Klein-Robbenhaar G, et al. Effects of adrenalectomy
and chronic adrenal corticosteroid replacement on potassium transport in rat
kidney. J Clin Invest. 1985;75(4):1317-1326.
Sur S, Camara M, Buchmeier A, Morgan S, Nelson HS. Double-blind trial of
pyridoxine (vitamin B6) in the treatment of steroid-dependant asthma. Ann
Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and
safety. Am J Clin Nutr. 1999;69:842-856.
Weryha G, Klein M, Guillemin F, Leclere J. [Corticosteroid osteoporosis in
the adult]. Presse Med. 1998;27(32):1641-1646.
Wilson JD. Vitamin deficiency and excess. In: Fauci AS, Braunwald E,
Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine.
14th ed. New York: McGraw-Hill Companies Health Professional
Yunice, AA, Czerwinski AW, Lindeman RD. Influence of synthetic
corticosteroids on plasma zinc and copper levels in humans. Am J Med Sci.
Copyright © 2000 Integrative Medicine
CommunicationsThis publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
responsibility for the accuracy of the information or the consequences arising
from the application, use, or misuse of any of the information contained herein,
including any injury and/or damage to any person or property as a matter of
product liability, negligence, or otherwise. No warranty, expressed or implied,
is made in regard to the contents of this material. No claims or endorsements
are made for any drugs or compounds currently marketed or in investigative use.
The reader is advised to check product information (including package inserts)
for changes and new information regarding dosage, precautions, warnings,
interactions, and contraindications before administering any drug, herb, or
supplement discussed herein.